Methods and systems for non-invasive treatment of tissue using high intensity focused ultrasound therapy

ABSTRACT

Methods and systems for non-invasive treatment of tissue using high intensity focused ultrasound (“HIFU”) therapy. A method of non-invasively treating tissue in accordance with an embodiment of the present technology, for example, can include positioning a focal plane of an ultrasound source at a target site in tissue. The ultrasound source can be configured to emit HIFU waves. The method can further include pulsing ultrasound energy from the ultrasound source toward the target site, and generating shock waves in the tissue to induce boiling of the tissue at the target site within milliseconds. The boiling of the tissue at least substantially emulsifies the tissue.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application claims the benefit of pending U.S. ProvisionalApplication No. 61/323,230, entitled “METHODS AND SYSTEMS FORNON-INVASIVE TREATMENT OF TISSUE USING HIGH INTENSITY FOCUSED ULTRASOUNDTHERAPY,” filed Apr. 12, 2010, and incorporated herein by reference inits entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This disclosure was made with government support under grant numberEB007643 awarded by National Institutes of Health (NIH)-FederalReporting and grant number SMST01601 awarded by National SpaceBiomedical Research Institute (NSBRI). The government has certain rightsin the invention.

TECHNICAL FIELD

The present technology relates generally to high intensity focusedultrasound. In particular, several embodiments are directed towardmethods and systems for non-invasive treatment of tissue using highintensity focused ultrasound therapy.

BACKGROUND

Minimally invasive and non-invasive therapeutic ultrasound treatmentscan be used to ablate, necrotize, and/or otherwise damage tissue. Highintensity focused ultrasound (“HIFU”), for example, is used to thermallyor mechanically damage tissue. HIFU thermal treatments increase thetemperature of tissue at a focal region such that the tissue quicklyforms a thermally coagulated treatment volume. HIFU treatments can alsocause mechanical disruption of tissue with well-demarcated regions ofmechanically emulsified treatment volumes that have little remainingcellular integrity. For certain medical applications, tissueemulsification may be more favorable than thermal damage because itproduces liquefied volumes that can be more easily removed or absorbedby the body than thermally coagulated solid volumes.

HIFU treatments can utilize a sequence of pulses, rather thancontinuous-wave HIFU exposures, to reduce undesirable thermal effects onthe surrounding tissue. In histotripsy exposures, for example, HIFUsources operate with low duty cycles (e.g., 1%), use relatively shortpulses (e.g., 10-20 microseconds), and deliver high pulse averageintensities of up to 40 kW/cm² to form bubbles that mechanically disrupttissue. Histotripsy techniques, for example, can induce cavitation bydelivering pulses of high peak negative pressures that are significantlyhigher than the tensile strength of the tissue. The repetition of suchpulses can increase the area of tissue affected by cavitation to createa “cavitation cloud” that emulsifies the tissue. Cavitation, however, isgenerally stochastic in nature, making cavitation-based HIFU treatmentssomewhat unpredictable and difficult to reproduce. For example,cavitation activity can stop unexpectedly during the course of thetreatment, resulting in the extinction of the cavitation cloud andtermination of the desired tissue emulsification. Very high peaknegative pressures of about −20 MPa are required to initiate andmaintain the cavitation cloud. To reach these peak negative pressurelevels, large aperture transducers with high focusing angles and highpower output capabilities are necessary. Therefore, there is a need toenhance the reliability, predictability, and consistency of mechanicaldisruption of tissue damage (e.g., emulsification), while operating atlower pressure levels and still limiting thermal coagulation of thetarget tissue and the surrounding tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic view of a HIFU system configured in accordancewith an embodiment of the present technology.

FIG. 1B is a graph illustrating focal pressure waveforms modeled intissue in accordance with several embodiments of the present technology.

FIG. 1C is a graph illustrating fluctuations in HIFU source drivevoltage in accordance with an embodiment of the present technology.

FIG. 1D is a graph illustrating acoustic signals received by a passivecavitation detection system during a HIFU treatment in accordance withan embodiment of the present technology.

FIG. 2 is a block diagram illustrating a method of treating tissue at atarget site in accordance with an embodiment of the present technology.

FIGS. 3A-3C are photographs of various types of lesions formed in tissueusing HIFU in accordance with embodiments of the present technology.

FIG. 4A-4C illustrate various lesions formed in tissue using HIFU inwhich duty cycle, pulse length, and power, respectively, were varied inaccordance with embodiments of the present technology.

DETAILED DESCRIPTION

The present technology is directed toward methods and systems fornon-invasively treating tissue using HIFU. In several embodiments, forexample, a HIFU pulsing protocol can generate shock waves at a targetsite that induce millisecond boiling to mechanically damage tissue withlittle to no thermal effect. The pulsing protocol can take into accountpeak positive pressure, shock wave amplitude, ultrasound frequency,pulse repetition frequency, pulse length, duty cycle, and/or otherfactors that induce mechanical fractionation of tissue. Additionally,HIFU systems and methods in accordance with the present technology candetect boiling and/or tissue erosion to identify and differentiatemechanical effects from thermal effects of HIFU treatment. These HIFUsystems and methods have a number of both therapeutic and cosmeticapplications, such as producing bulk ablation of benign and malignanttumors.

Certain specific details are set forth in the following description andin FIGS. 1A-4C to provide a thorough understanding of variousembodiments of the technology. For example, several embodiments of HIFUtreatments that destroy tissue are described in detail below. Thepresent technology, however, may be used to destroy multi-cellstructures similar to tissue. Additionally, the term “target site” isused broadly throughout the disclosure to refer to any volume or regionof tissue that may benefit from HIFU treatment. Other details describingwell-known structures and systems often associated with ultrasoundsystems and associated devices have not been set forth in the followingdisclosure to avoid unnecessarily obscuring the description of thevarious embodiments of the technology. A person of ordinary skill in theart, therefore, will accordingly understand that the technology may haveother embodiments with additional elements, or the technology may haveother embodiments without several of the features shown and describedbelow with reference to FIGS. 1A-4C.

FIG. 1A is a schematic view of a HIFU system 100 configured inaccordance with an embodiment of the present technology. The HIFU system100 can include a HIFU source 102 operably coupled to a functiongenerator 104 and an amplifier. The HIFU source 102 can be an ultrasoundtransducer that emits high levels of ultrasound energy to a focus 120.The focus 120 can be a point, plane, or region at which the intensityfrom the HIFU source 102 is the highest. In other embodiments, the HIFUsource 102 can include a single-element device, a multi-element device,an extracorporeal device, an intracavitary device, and/or other devicesor systems configured to emit HIFU energy to a focus. The HIFU source102 can have a frequency range of approximately 0.5-20 MHz. In otherembodiments, the frequency of the HIFU source 102 can vary. The functiongenerator 104 (e.g., an Agilent 33250A function generator from Agilentof Palo Alto, Calif.) and the amplifier 106 (e.g., an ENI A-300 300 W RFamplifier from ENI of Rochester, N.Y.) can drive the HIFU source 102 togenerate pulsed shock waves proximate to the focus 120. Accordingly, theHIFU system 100 can implement a pulsing protocol in which ultrasoundfrequency, pulse repetition frequency, pulse length, duty cycle,pressure amplitude, and/or other factors associated with the HIFUtreatment can be adjusted to generate shock waves proximate to the focus120.

Without being bound by theory, it was generally thought that shock wavescould not form in tissue due to the losses in amplitude caused by thedegradation of focusing in inhomogeneous tissue and the rapid absorptionof higher harmonic frequencies in the tissue along the propagation pathbetween a target and an ultrasound source. However, the presentinventors have shown that shock waves can, in fact, form within tissuewhen used with suitable HIFU systems (e.g., the HIFU system 100). FIG.1B, for example, is a graph illustrating modeled focal waveform levelsin tissue produced by the HIFU system 100. The HIFU system 100 candeliver pulsed high intensities (e.g., between approximately 6 kW/cm²and 15 kW/cm²) at the focus 120 to generate shock waves havingamplitudes greater than approximately 30 MPa. In other embodiments, theshock wave amplitudes and intensities of the HIFU system 100 can begreater or smaller. Advantageously, the shock waves can enhance heatingof the tissue to induce rapid boiling.

Referring back to FIG. 1A, during treatment the HIFU source 102 can bepositioned proximate to a tissue 108, and the focus 120 of the HIFUsource 102 can be aligned with at least a portion of a target site 122within the tissue 108. For example, the HIFU source 102 can bepositioned over a patient's kidney, heart, or liver, and the focus 120can be aligned with infected or otherwise adverse tissue therein. Largertarget sites 122 can be mechanically fractionated by scanning the HIFUsource 102 over the treatment region using either mechanical orelectronic scanning Such scanning and the initial positioning of theHIFU source 102 can be performed manually or mechanically (e.g., using athree-axis positioning system, not shown). The function generator 104can initiate the pulsing protocol to generate shock waves withamplitudes between approximately 30 MPa and approximately 80 MPa at thefocus 120 with the HIFU source 102 having a frequency of approximately 2MHz. In other embodiments, such as at lower or higher ultrasoundfrequencies, the shock wave amplitudes of the HIFU source 102 can begreater or smaller. Absorption of ultrasonic energy occurs primarily atthe shock front (e.g., shown in FIG. 1B), and induces rapid heating ofthe tissue 108 that can boil the tissue 108 within milliseconds. Forexample, the amplitude of the shock wave can be such that it causestissue boiling in less than 10 ms. Depending upon the power driving theHIFU system 100 and/or the acoustic parameters of the tissue 108, thetime-to-boil can be greater or less than 10 ms.

The HIFU system 100 can be configured such that the duration of eachpulse is at least equivalent to the time necessary to induce tissueboiling at approximately 100° C. Therefore, during each pulse, one ormore boiling bubbles can be formed in the tissue 108. In severalembodiments, the boiling bubbles can have cross-sectional dimensions ofapproximately 2-4 mm when the ultrasound frequency is approximately 2MHz. In other embodiments, however, the boiling bubbles can be larger orsmaller. For example, the boiling bubbles in the tissue 108 can have across-sectional dimension between approximately 100 μm and approximately4 mm on the order of the beam-width of the ultrasound source 102 at thefocus 120. The superheated vapor of the boiling bubbles provides a forcepushing outward from the bubble. This repetitive explosive boilingactivity and interaction of the ultrasound shock waves with the boilingbubbles emulsifies the tissue 108 at the target site 122 to form aliquid-filled lesion devoid of cellular structure, with little to nothermal coagulation within the treated region. The reflection of theshock wave from the surface of these millimeter-sized boiling bubblescan also form cavitation bubbles proximate to the boiling bubble thatcan also induce mechanical damage to tissue.

Mechanical tissue destruction can occur consistently within localizedtreatment volumes when the temperature of the tissue reaches 100° C. andboiling bubbles form during each pulse or after a series of consecutivepulses. For example, boiling bubbles are generally produced proximate tothe focus 120 of the HIFU source 102 (i.e., where shock wave amplitudeis the highest), unlike cavitation that occurs randomly over a largerregion. In selected embodiments, the energy deposition of the ultrasoundbeam can focus within 100 microns of the target site 122. Additionally,unlike peak negative pressures that induce cavitation and continuouslygrow the treatment volume, the peak positive pressures that induceboiling bubbles can maintain relatively defined treatment volumes.Moreover, the present method of using shock waves to rapidly heat tissueto boiling allows the HIFU system 100 to penetrate target sites deeperwithin the tissue 108 than cavitation-based HIFU techniques that requirehigher pressures to deliver to the focus through absorptive tissue.Boiling bubbles can also be much larger (e.g., approximately 2-4 mm)than individual cavitation bubbles that must randomly coalesce toproduce any beneficial treatment volume. Therefore, the shock waveheating and millisecond boiling generated by the HIFU system 100provides a highly repeatable, localizable, and predictable mechanicaldestruction of the tissue 108 at lower pressure levels as compared tocavitation.

In selected embodiments, the pulsing protocol of the HIFU system 100 canbe adjusted to minimize the deposition of the HIFU energy in the tissue108, and thereby reduce the thermal effects (e.g., thermal coagulation,necrotized tissue) of the HIFU treatment. For example, repeating shockwaves at a pulse repetition frequency that is slow enough (e.g.,approximately 1 Hz or 1% duty cycle) to allow cooling between the pulsessuch that lesion content within the target site 122 and the surroundingtissue 108 shows minimal to no evidence of thermal denature. A dutycycle of less than approximately 10% also allows cooling between pulsesthat minimizes thermal denature. In selected embodiments, the durationof the pulses can be reduced over the course of the pulsing protocol toaccount for a decreasing time to boil caused by the retention of heat inthe tissue 108 between pulses. Additionally, the duration of each pulsecan be such that the thermally denatured volume of the tissue 108 withineach pulse is negligible. For example, in selected embodiments, theduration of each pulse is less than approximately 10 ms. In otherembodiments, the pulse length can be longer.

The HIFU system 100 can also include systems or devices that detect andmonitor boiling initiation and the bubble activity in the tissue 108.These devices can be used during treatment to distinguish boilingbubbles from cavitation bubbles and ensure the pulsing protocol inducesthe desired boiling bubbles at the target site 122. In the embodimentillustrated in FIG. 1A, for example, the HIFU source 102 is operablycoupled to a voltage probe 110 and an oscilloscope 112 that can monitorand record, respectively, the drive voltage at the HIFU source 102. FIG.1C is a graph illustrating a recorded drive voltage during HIFUtreatment in accordance with an embodiment of the present technology.Fluctuations in the drive voltage indicate the onset of boiling bubblesand can be distinguished from lower levels of fluctuations that arecaused by cavitation activity. In the embodiment illustrated in FIG. 1C,the drive voltage begins to fluctuate within 10 ms of the HIFU pulse,and thus indicates the presence of boiling bubbles within 10 ms of theHIFU pulse. In other embodiments, the time-to-boil can be shorter orlonger.

Referring back to FIG. 1A, the HIFU system 100 can also include apassive cavitation detector (“PCD”) 124 that monitors acoustic signalsassociated with boiling. For example, the PCD 124 can include anacoustic receiver (e.g., an ultrasound transducer) separate from theHIFU source 102, but confocally aligned with the focus 120 of the HIFUsource 102 such that the PCD 124 can receive real-time acoustic feedbackduring HIFU treatment. In general, boiling bubbles scatter frequenciesthat already exist in the incident wave, whereas cavitation bubblescreate short pops when they collapse and have a broadband frequencynoise. Boiling bubbles may also generate lower frequency noise (e.g.,kilohertz frequencies) that can be recorded and used to monitortreatments. As shown in FIG. 1A, similar to the voltage probe 110, thePCD 124 can also be coupled to the oscilloscope 112 to record acousticsignals during HIFU treatment. FIG. 1D, for example, is a graphillustrating acoustic signals during HIFU treatment in accordance withan embodiment of the present technology. The graph shows that a largechange in the PCD signal amplitudes caused by boiling bubbles, beginwithin 10 ms of the first HIFU pulse. In other embodiments, however, theboiling bubbles can occur sooner or later during the HIFU pulse.

Echogenic boiling activity and/or the thermal effects of the HIFUtreatment can also be monitored using separate devices and systems. TheHIFU system 100 illustrated in FIG. 1A, for example, includes an imagingsystem 114 that can create a visual image to monitor the boiling bubblesand thus temperatures of approximately 100° C. in real-time at a depthwithin the tissue 108. The imaging system 114 can be a separate confocaltransducer, an unfocused transducer, another type of confocal orunfocused ultrasound source, one or more sub-element(s) of amulti-element array, and/or a separate imaging system. For example, inone embodiment the imaging system 114 includes an HDI-1000 scanner witha CL 10-5 scanhead made by Philips Medical Systems of Bothell, Wash. Inother embodiments, the imaging system 114 can include a magneticresonance imaging (“MRI”) system that can monitor temperature andboiling activity during HIFU treatments.

Additionally, as shown in FIG. 1A, the HIFU system 100 can include ahigh-speed camera 116 (e.g., video, still frame) that can take video orstill images of the target site 122 during HIFU treatment to capture theeffects of the HIFU treatment on the tissue 108. Such a camera 116 mustgenerally be used with initially transparent tissues or tissue phantomsto capture the thermal effects of HIFU treatment within the tissue 108.Accordingly, the high-speed camera 116 can be especially suited forexperiments and testing that include transparent gel phantoms tosimulate tissue.

The HIFU system 100 can also simulate the shock waves and heating inwater or tissue. Resultant modeling can be used to calculate heatingfrom the shock amplitude of the focal waveform, and for extrapolatingpressure waveforms at the focus 120 in water to the equivalent waveformsin tissue. One such method for this extrapolation is called “derating,”and is useful for regulatory oversight and HIFU treatment planning. Forexample, derating can be used to determine values of the acoustic fieldparameters in the tissue region exposed to HIFU (e.g., the target site122 and the surrounding tissue 108). During the derating process, lowlevel ultrasound measurements can be taken at the focus 120 in water andscaled to the higher level outputs used during therapeutic HIFUtreatments. To obtain in situ acoustic parameters, the correspondingvalues in water are scaled to account for losses that occur over thepropagation path in tissue. This derating procedure assumes linear wavepropagation both in water and in tissue. However, the high acousticintensities associated with the present HIFU system 100 cause nonlinearpropagation effects that cause the formation of shock was in the focus120 (i.e., where the pressure is the highest) of the HIFU source 102. Assuch, the nonlinear propagation can be taken into account by comparingthe pressures at the HIFU source 102 that produce the same focalwaveforms calculated or measured in water and in tissue. The linearattenuation in the tissue at the source frequency can provide a scalingfactor that accounts for losses over the wave propagation in tissue.This scaling factor can be used to determine optimal parameters (e.g.,peak positive pressure) of the pulsing protocol to achieve controlledtissue emulsification. U.S. Provisional Application No. 61/384,108,entitled “A DERATING METHOD FOR THERAPEUTIC APPLICATIONS OF HIGHINTENSITY FOCUSED ULTRASOUND,” filed Sep. 17, 2010, further disclosessuch a derating method, and is incorporated herein by reference in itsentirety.

The derating process in conjunction with the HIFU system 100 canimplement a refined pulsing protocol that mechanically damages tissue,while minimizing thermal denature. For example, the requisite power foreffective HIFU treatment can be calculated for different parts of thebody by taking into account the type of tissue (e.g., the losses ofultrasound energy in the tissue prefocally) and the size of theultrasound source 102. As such, the HIFU system 100 can be used toemulsify malignant or benign tumors in the prostate, kidneys, and/orother body parts. The HIFU system 100 can also be used to cut throughtissue. For example, the localized HIFU treatment can cut through theheart septum to non-invasively treat heart defects. In otherembodiments, the HIFU system 100 can be used to treat other tissueswithin the body.

FIG. 2 is a block diagram illustrating a method 200 of treating a targettissue site in accordance with an embodiment of the present technology.The method 200 can include providing a pulsing protocol (block 202). Asdiscussed above, pulsing protocols can include a variety of differentfactors that can induce millisecond boiling with little to no thermaldenature in and around the lesion. For example, a pulsing protocol cantake into account the ultrasound frequency at a HIFU source, peakpositive pressure at the focus, shock amplitude, pulse length, pulserepetition frequency, and duty cycle. In other embodiments, additionalfactors related to tissue boiling and shock wave heating can be includedin the pulsing protocol. In selected embodiments, a derating process canbe used to estimate values of acoustic field parameters of the exposedtissue, and therefrom calculate the requisite peak positive pressuresand pulse lengths for shock wave heating and millisecond boiling. Thepulsing protocol can also be configured to minimize thermal effects ofthe HIFU treatment on the tissue. For example, as described above, theduty cycle can be less than 10% to ensure sufficient cooling occursbetween shock wave pulses and prevent thermal denature. As anotherexample, the pulse length can be less than approximately 100 ms suchthat any thermally denatured volume formed within each pulse isnegligible.

Once the pulsing protocol is established, the method 200 can continue bypositioning a focus of a HIFU source proximate to a target site in atissue (block 204). The HIFU source can include generally similarfeatures as the HIFU source 102 described above with reference to FIG.1A. For example, the HIFU source can generate shock waves at the focuswith amplitudes between approximately 30 MPa and approximately 80 MPafor ultrasound sources operating at frequencies of approximately 2 MHz.In other embodiments, the shock waves can have amplitudes betweenapproximately 10 MPa and approximately 100 MPa for ultrasound sourcesthat have frequencies between approximately 0.5-20 MHz. As discussedabove, the focus of the HIFU source can be mechanically or manuallyaligned with the target site.

Optionally, the method 200 can include delivering at least one pulse ofultrasound energy from the HIFU source to the tissue (block 206), andmonitoring the target site in real-time during and/or after the pulse(block 208). For example, a test pulse can be delivered to the targetsite, and the drive voltage and/or the acoustic signal can beinterpreted to determine whether the requisite millisecond boilingoccurred. Fluctuations in the drive voltage monitored by a voltage probeand/or scattered frequencies of the acoustic signal recorded by a PCDsystem or other acoustic receivers can indicate that the desired boilingbubbles are generated during HIFU treatment (i.e., acoustic pulsing). Inother embodiments, images of the target site can be taken during thetest pulse with a B-mode ultrasound transducer and/or other imagingsystems to visually identify the thermal effects at the target site.When boiling is not identified during the test pulse and/or thermaldestruction occurs, the method 200 can continue by adjusting the pulsingprotocol such that it induces boiling during substantially every pulse(block 210). For example, the pulse length, and/or the power can beincreased to ensure boiling during each pulse. As another example, theduty cycle, pulse length, and/or shock wave amplitude at the focus canbe decreased to prevent thermal tissue destruction (e.g., coagulation).

The method 200 can continue by pulsing ultrasound energy toward thetarget site in the tissue (block 212). Each pulse of shock waves at thetarget site can generate boiling bubbles within milliseconds. Forexample, shock waves with amplitudes between approximately 30 MPa andapproximately 80 MPa delivered at a HIFU source frequency ofapproximately 2 MHz, and a peak power between approximately 10-25 kW caninduce boiling bubbles within 10 ms. This rapid millisecond boiling canmechanically disrupt the tissue without evident thermal damage. Forexample, the pulse lengths can be short enough (e.g., belowapproximately 40 ms) to substantially prevent thermally denature withinor around the lesion. Additionally, as described above, the HIFU sourcecan deliver shock waves to its focus to consistently induce boilingwithin a localized treatment area. Therefore, the millisecond boilingprovided by this HIFU method 200 provides a repeatable, localizable, andpredictable mechanical destruction of tissue. Optionally, the targetsite can be monitored during HIFU treatment to ensure boiling and/orotherwise observe the effects of the HIFU treatment (block 216). Themethod 200 can continue until the desired target site is mechanicallyfractionated or otherwise destroyed.

FIGS. 3A-3C are photographs of various types of lesions 350 (identifiedindividual as a first lesion 350 a, a second lesion 350 b, and a thirdlesion 350 c) formed in tissue 308 using a pulsing protocol inaccordance with embodiments of the present technology. The lesions 350were produced with an ultrasound source operating at a frequency ofapproximately 2 MHz and a total “HIFU on” duration of approximately 500ms and a constant power to a HIFU source within each pulse. FIGS. 3A-3Cshow the progressive increase of the pulse duration (e.g., between 200microseconds and 500 milliseconds) and/or duty cycle (between 0.3% and100%). Purely mechanical damage occurred with duty cycles ofapproximately 2% or less and pulse durations of less than 30 ms (i.e.,3-10 times the time-to-boil). For example, the first lesion 350 a shownin FIG. 3A illustrates purely mechanical damage that includes a cavityor void filled with liquefied tissue (for clarity, liquefied tissue isremoved). The liquid is the same color as the unaffected tissue 308, andcan be easily poured from the void.

Increasing the duty cycle and/or the pulse duration of the pulsingprotocol can result in the second lesion 350 b shown in FIG. 3B thatincludes a combination of mechanical and thermal damage. The secondlesion 350 b includes a void similar to that of the first lesion 350 a,but is filled with a white paste. Like the liquefied tissue of the firstlesion 350 a, the white paste can be easily removed from the void.Additionally, as shown in FIG. 3B, the second lesion 350 b hascoagulated edges 352 (e.g., indicated by the lighter tissue). Both thewhite paste that fills the void and the coagulated edges 354 indicatethat the thermal exposure during HIFU treatment was too long to avoidthermal tissue damage. Further increasing the pulse duration and/or dutycycle can result in the third lesion 350 c shown in FIG. 3C. The thirdlesion 350 c is a solid thermal lesion with coagulated edges 352 and anevaporated core. In this embodiment, the purely thermal damages to thetissue 308 occurred with pulses longer than 100 ms or a duty cycleexceeding approximately 10%.

As further shown in FIGS. 3A-3C, the lesions 350 can form a tadpole-likeshape. The focus of the HIFU source (e.g., the HIFU source 102 shown inFIG. 1A) is generally at the “tail” end of the lesion 350 and the largercavity or void is oriented closer to the HIFU source.

FIGS. 4A-4C illustrate lesions formed in tissue 408 (e.g., liver andheart tissue) using HIFU treatments which vary duty cycle, pulse length,and power, respectively, in accordance with embodiments of the presenttechnology. More specifically, FIG. 4A illustrates various lesions 450(identified individually as first through fifth lesions 450 a-e,respectively) formed in liver tissue using HIFU treatments in which theduty cycle was varied between 1% and 100% (i.e., continuous exposure)with a mean time to boil of approximately 3.7 ms. As with the lesions350 described above with reference to FIGS. 3A-3C, as the duty cycleincreases, the lesions contained increasing amounts of thermal damage(e.g., coagulation, white paste) with less evident mechanical damage.

FIG. 4B illustrates various lesions 460 (identified individually asfirst through fourth lesions 460 a-d, respectively) formed in hearttissue using HIFU treatments in which the pulse length was variedbetween 10 ms and 100 ms. The duty cycle was maintained at 1%, and thetotal HIFU treatment time was 500 ms. Boiling was generally induced atapproximately 3.3 ms. As shown in FIG. 4B, even though the pulse lengthincreased, the damage induced to the tissue 408 was mostly mechanical asevidenced by the minimal amount of blanched tissue surrounding thelesions 460.

FIG. 4C illustrates various lesions 470 formed in tissue using HIFUtreatments in which the power to the HIFU source was varied such thatthe focal waveform was changed from a non-linearly distorted waveform toa full shock wave. As shown in FIG. 4C, the non-linearly distorted wavewith an intensity of 6,000 W/cm² did not form a lesion. However,increasing the power to form shock waves did cause mechanical damageshown as the lesions 470. Additionally, in this embodiment, the peakpositive pressure was changed from 36 MPa to 70 MPa, while the peaknegative pressure was steadily maintained (i.e., between 9 and 12 MPa)at a pressure lower than that necessary to induce cavitation damage totissue. Thus, FIG. 4C shows that the shock waves with amplitudes mainlydefined by peak positive pressures were the source of mechanical tissuedamage, rather than cavitation.

From the foregoing, it will be appreciated that specific embodiments ofthe technology have been described herein for purposes of illustration,but that various modifications may be made without deviating from thedisclosure. For example, the HIFU system 100 of FIG. 1A can includeadditional devices and/or systems to facilitate shock wave heating andmillisecond boiling of the tissue 108. For example, the HIFU system 100can include a timing board to trigger the function generator 104,additional amplifiers 106, high-pass or other suitable filters, acomputer to drive the entire HIFU system 100, and/or other suitabledevices related to HIFU treatments. Certain aspects of the newtechnology described in the context of particular embodiments may becombined or eliminated in other embodiments. For example, the HIFUsystem 100 does not need to include some of the devices shown in FIG.1A. In selected embodiments, the HIFU system can include only one of ora combination of the voltage probe 110, the PCD 124, the imaging system114, and/or the high-speed camera 116 to monitor the thermal andmechanical effects of the HIFU treatment. Additionally, while advantagesassociated with certain embodiments of the new technology have beendescribed in the context of those embodiments, other embodiments mayalso exhibit such advantages, and not all embodiments need necessarilyexhibit such advantages to fall within the scope of the technology.Accordingly, the disclosure and associated technology can encompassother embodiments not expressly shown or described herein. Thus, thedisclosure is not limited except as by the appended claims.

1-21. (canceled)
 22. A high intensity focused ultrasound (HIFU) systemfor treating tissue, the HIFU system comprising: an ultrasound sourcehaving a frequency range between approximately 0.5 MHz and approximately20 MHz, the ultrasound source being configured to deliver a peakpositive pressure of greater than approximately 10 MPa; and a functiongenerator operably coupled to the ultrasound source, the functiongenerator being configured to generate a pulsing protocol delivered bythe ultrasound source to a target site of tissue, wherein the pulsingprotocol comprises at least one of ultrasound source frequency, peakpositive pressure, pulse length, shock wave amplitude, pulse repetitionfrequency, and duty cycle.
 23. The HIFU system of claim 22 wherein theultrasound source is configured to generate shock waves proximate to thetarget site in the tissue.
 24. The HIFU system of claim 22, furthercomprising a monitoring system configured to distinguish boiling fromcavitation in the tissue.
 25. The HIFU system of claim 24, furthercomprising a controller operably coupled to the ultrasound source andthe function generator, wherein the controller is configured to adjustthe pulsing protocol during treatment in response to feedback from themonitoring system to induce boiling during each pulse with substantiallyno thermal damage to the tissue at the target site and surrounding thetarget site.
 26. The HIFU system of claim 24 wherein the monitoringsystem comprises an imaging device configured to detect hyperechoicimages in the tissue.
 27. The HIFU system of claim 24 wherein themonitoring system comprises a voltage probe configured to detectfluctuations in drive voltage of the ultrasound source.
 28. The HIFUsystem of claim 24 wherein the monitoring device system comprises apassive cavitation detector (PCD) having a focus aligned with a focus ofthe ultrasound source, the focus being configured to detect changes inacoustic signals related to boiling.
 29. The HIFU system of claim 24wherein the monitoring system comprises a magnetic resonance imagingsystem configured to detect temperature and boiling activity at thetarget site.
 30. The HIFU system of claim 24 wherein the monitoringsystem comprises an ultrasound imaging device configured to send andreceive signals that detect the presence of bubbles in the tissue. 31.The HIFU system of claim 24 wherein the monitoring system is configuredto detect the presence of boiling bubbles in the tissue.
 32. The HIFUsystem of claim 22 wherein the pulsing protocol comprises peak positivepressure and the peak positive pressure is a result of nonlinearpropagation of the HIFU waves, resulting in the shock waves that atleast substantially emulsify the tissue at the target site.
 33. The HIFUsystem of claim 23 wherein the peak positive pressure is less than orequal to approximately 100 MPa.
 34. The HIFU system of claim 23 whereinthe peak positive pressure is greater than approximately 100 MPa.
 35. Amethod for treating tissue with high intensity focused ultrasound(HIFU), the method comprising: generating, from an ultrasound source,HIFU waves having a frequency range between approximately 0.5 MHz andapproximately 20 MHz and a peak positive pressure of greater thanapproximately 10 MPa; and generating a pulsing protocol used by theultrasound source to apply the HIFU waves to a target site of tissue,wherein the pulsing protocol defines at least one of ultrasound sourcefrequency, peak positive pressure, pulse length, shock wave amplitude,pulse repetition frequency, and duty cycle.
 36. The method of claim 35wherein the generated HIFU waves are configured to generate shock wavesin tissue at the target site.
 37. The method of claim 36 wherein thepeak positive pressure is a result of nonlinear propagation of the HIFUwaves resulting in the shock waves that at least substantially emulsifythe tissue at the target site.
 38. The method of claim 35, furthercomprising monitoring to distinguish boiling from cavitation in thetissue at the target site.
 39. The method of claim 38, wherein themonitoring comprises detecting the presence of boiling bubbles in thetissue.
 40. The method of claim 38 wherein the monitoring comprisessending and receiving signals, using an ultrasound imaging device, thatdetect the presence of bubbles in the tissue.
 41. The method of claim 38wherein the monitoring comprises detecting hyperechoic images in imagesof the tissue.
 42. The method of claim 36 wherein the monitoringcomprises detecting, using a voltage probe, fluctuations in drivevoltage of the ultrasound source.
 43. The method of claim 38 wherein themonitoring comprises aligning a focus of a passive cavitation detectorwith a focus of the ultrasound source to detect changes in acousticsignals related to boiling.
 44. The method of claim 38 wherein themonitoring comprises detecting temperature and boiling activity at thetarget site using a magnetic resonance imaging system.
 45. The method ofclaim 38, further comprising adjusting, in response to feedback from themonitoring, the pulsing protocol during treatment, wherein theultrasound waves generated as a result of the adjusted pulsing protocolinduce boiling during each pulse.
 46. The method of claim 45 whereininducing boiling during each pulse causes substantially no thermaldamage to the tissue at and surrounding the target site.
 47. The methodof claim 35 wherein the peak positive pressure is less than or equal toapproximately 100 MPa.
 48. The method of claim 35 wherein the peakpositive pressure is greater than approximately 100 MPa.
 49. A highintensity focused ultrasound (HIFU) apparatus for treating tissue, theHIFU apparatus comprising: an ultrasound source configured to deliver apeak positive pressure of greater than approximately 10 MPa; and afunction generator operably coupled to the ultrasound source, thefunction generator being configured to generate a pulsing protocoldelivered by the ultrasound source to a target site of tissue, whereinthe pulsing protocol comprises at least one of ultrasound sourcefrequency, peak positive pressure, pulse length, shock wave amplitude,pulse repetition frequency, and duty cycle.